Neurofascin

Neurofascin (NFASC) is a cell adhesion protein and ankyrin-binding molecule involved in neurite extension, axonal guidance, synaptogenesis, myelination, and neuron-glial interactions (UniProt: O94856). The protein is expressed in neural tissues where it mediates structural organization and cellular communication critical for nervous system development and function.

Neurofascin is associated with neurodevelopmental disorder with central and peripheral motor dysfunction (NEDCPMD, MIM 618356), an autosomal recessive condition characterized by hypotonia, developmental delay, progressive ataxia, and demyelinating peripheral neuropathy (UniProt: O94856). This disease link underscores the protein's importance in neuronal and glial integrity.

In Alzheimer's disease, neurofascin is upregulated in human post-mortem AD brain tissue compared to age-matched controls (mean log2FC = 0.1097; Chaparral AD proteomics). The modest increase was detected across subcellular fractions in a TMT-labeled proteomics study, suggesting potential involvement in AD-related pathology, though the biological significance of this mild elevation remains to be determined.